propranolol INDERAL
Class: Beta Blocker/Class II AntiarrhythmicFDA Indications: Hypertension, Essential Tremor, Obstructive Hypertrophic Cardiomyopathy, Pheochromocytoma, Post-MI Mortality Reduction, Stable Angina, Supraventricular Tachycardia, Tachyarrhythmias
Off-Label Use: Akathisia, Performance Anxiety, Supraventricular Tachycardia, Thyroid Storm, Thyrotoxicosis, Lithium-induced Tremor, Variceal Hemorrhage (prophylaxis), Tetralogy Of Fallot Hypercyanotic Spells, Aggression, Panic Disorder, Social Anxiety, Essential Tremor
Prescribing
Forms: 10, 20, 40, 60, 80mg tablet; 60, 80, 120, 160mg Extended-Release Capsule (Inderal LA)Dose Range: 20-320 mg/day
Starting: Akathisia: 10 mg bid-tid; Performance anxiety: 40 mg 60-90 min prior to anxiety-provoking event; Lithium-induced tremor: 30-80 mg/day in divided doses
Precautions
Contraindications: Uncompensated CHF (unless the failure is d/t tachyarrhythmias being treated with propranolol), cardiogenic shock; severe sinus bradycardia, sick sinus syndrome, or heart block greater than 1° (except in patients with a functioning artificial pacemaker); bronchial asthmaSide Effects: cold extremities, sexual dysfunction, insomnia, nightmares, dizziness, confusion
Pharmacodynamics
1° MOA: Nonselective β-adrenergic blocker; competitively blocks response to β1- and β2-adrenergic stimulation which results in ↓ heart rate, myocardial contractility, blood pressure, & myocardial O2 demand2° MOA: Presynaptic 5HT1A
Target: β1, β2
Pharmacokinetics
t½: 4 (3-6)° TMAX: 1-4°Substrate of: 1A2, 2D6; 2C19, 3A4
Inhibits: 1A2 (weak); Induces: ∅
Active Metabolites: 4-hydroxypropranolol (t½ 5.2-7.5°)
DDIs
- - 1A2 and 2D6 inhibitors can ↑ levels; 1A2 and 2D6 inducers can ↓ levels
- - caution when co-prescribed with other medications that can lower blood pressure
Misc
- - t½: IR 3-6°; Extended-release 8-10°
- - lipophilic—readily enters the blood-brain barrier
- - it's thought to be most likely that propranolol aids in breaking the cycle of anxiety in which misappraisal of somatic sensations of sympathetic origin (i.e. palpitations, ↑'d ventilation) fuel the occurrence of panic
- - there's also evidence to suggest that after a fear memory is recollected, and followed specifically by a prediction error, propranolol selectively blocks protein synthesis, thereby prohibiting 'reconsolidation' of the fear memory
Special Populations
Category C—Apparently not a teratogen, but fetal and neonatal toxicity may occur. Some β-blockers may cause IUGR & ↓'d placental weight (treatment beginning early in the 2nd trimester results in the greatest weight reductions, whereas treatment restricted to the 3rd trimester primarily affects only placental weight)
RID 1%; the American Academy of Pediatrics classified propranolol as compatible with breastfeeding, though the American Academy of Pediatrics classified propranolol as compatible with breastfeeding, though nursing infants exposed to propranolol in breast milk should be closely observed for symptoms of β-blockade
Propranolol is one of the known orally-administered drugs that exhibits ↓ in first-pass metabolism with aging ∴ start low & taper cautiously
Studies have reported a delayed absorption rate and a reduced half-life of propranolol in patients with renal failure of varying severity. Use with caution.
Propranolol is extensively metabolized by the liver. Use with caution.